Occupation-Based Cognitive Stimulation With and Without Motivational Feedback in Parkinson's Disease (EOBCS)

Study objectives and hypotheses This trial aims to evaluate the effects of enjoyable occupation-based cognitive stimulation, with and without motivational feedback, on occupational performance, cognitive function, quality of life, functional mobility, and psychological symptoms (anxiety, apathy, fear-related constructs) in older adults with PD and cognitive impairment.

We hypothesize that:

Participants receiving cognitive stimulation with motivational feedback will demonstrate greater improvements in occupational performance, cognitive function, quality of life, and functional mobility than those receiving the same intervention without feedback.

Both intervention groups (with and without feedback) will show superior outcomes in occupational performance, cognition, and quality of life compared with conventional occupational therapy.

By integrating cognitive stimulation, enjoyment, and motivational mechanisms within an occupation-based framework, results from this study will be used to inform an intervention program and/or a larger-scale trial targeting non-motor symptoms in PD.

Methods and materials Trial design This study is a parallel, three-arm randomized controlled trial (RCT) with blinded outcome assessment. Participants will be randomized (1:1:1) to: (A) occupation-based cognitive stimulation with motivational feedback, (B) occupation-based cognitive stimulation without motivational feedback, or (C) conventional care. The trial follows a superiority design comparing both intervention arms and conventional care. Randomization will occur after baseline assessment, with blinded outcome assessors and participants blinded to study hypotheses. Study flow will follow the Consolidated Standards of Reporting Trials (CONSORT) guidelines, and the protocol was developed according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement.

Participants and recruitment procedures Participants will be community-dwelling older adults with PD recruited from movement disorder clinics and rehabilitation centers in Tehran, Iran, with additional recruitment facilitated through the Iran Parkinson Association. Eligible individuals will undergo an initial screening by the research team and will receive written and oral information regarding study objectives, procedures, assessments, and ethical considerations. Written informed consent will be obtained prior to enrollment.

To reduce variability related to medication effects, all assessments and intervention sessions will be conducted during the dopaminergic "ON" state, approximately one hour after levodopa administration. Levodopa equivalent daily dose (LEDD) will be calculated at each assessment using the standardized conversion method described by Tomlinson et al.

Data collection Data will be collected by a research assistant who is an occupational therapist with six years of experience in neurological rehabilitation. The assistant will conduct eligibility screening and all outcome assessments at predefined time points and will remain blinded to group allocation, study purpose, treatment delivery, and randomization procedures.

This study employs a single-blind design with blinded outcome assessment. Interventions will consist of 12 sessions delivered over 6 weeks (two sessions per week) by experienced occupational therapists (≥2 years of clinical experience) who are not involved in outcome assessment or data analysis. Participants will be blinded to group allocation and study hypotheses. To minimize contamination, groups will be scheduled in separate time blocks or on different days within the same facility, with no overlapping attendance. The study will be described in neutral terms (e.g., "comparing activity programs") without disclosing allocation, and participants will be instructed not to discuss session details. Assessment and intervention responsibilities will be strictly separated to reduce bias.

To ensure treatment fidelity, all therapists will complete standardized 4-hour training based on an intervention manual, participate in two supervised practice sessions, and receive weekly supervision. In addition, 20% of sessions will be monitored using a fidelity checklist.

Randomization and blinding After providing informed consent and completing baseline assessment, participants will be randomly assigned to one of three groups using a computer-generated sequence (www.randomizer.org) prepared by an independent researcher not involved in recruitment, assessment, or intervention delivery.

Allocation concealment will be ensured using sequentially numbered, sealed, opaque envelopes.

Outcome assessors will remain blinded to group allocation throughout the study. Participants will be blinded to group allocation and specific study hypotheses. Unblinding is not anticipated; however, if required, access to allocation codes will be restricted to the trial steering committee, and all unblinding events will be documented.

Sample size calculation Using G*Power for a 3 × 3 mixed factorial repeated measures ANOVA, an initial sample of 71 community dwelling older adults with PD and cognitive impairment was estimated based on the MCID of the COPM performance score (1.17 points), 80% power, two sided α = 0.05, and a 15% attrition rate informed by a scoping review of PD trials [16]. Because this effect size may not hold in our three-arm design, a futility analysis will be performed after 45 participants complete the post intervention assessment. The observed COPM effect size will be used to recalculate the required total sample size to maintain 80% power. The trial will be stopped for futility if the recalculated sample size exceeds 90 participants (our feasibility limit). Otherwise, the sample size will be adjusted accordingly, and recruitment will continue. No interim hypothesis testing will be conducted, and the type I error rate will remain at 0.05.

Interventions All participants will receive an explanation of the role and importance of therapy in PD. Interventions will be delivered twice weekly for 6 weeks (12 sessions), with each session lasting approximately 60 minutes. Sessions will be scheduled according to participant preference and medication regimen and will be conducted during the dopaminergic "ON" state. Rest breaks will be provided as needed. Participants will be instructed to refrain from other rehabilitation interventions during the study period, and participation may be discontinued at the participant's request.

All participants will be informed, in neutral terms, that their participation is crucial for helping the research team understand whether the treatment approaches being tested are helpful for individuals with PD. Interventions will be delivered twice weekly for 6 weeks (12 sessions), with each session lasting approximately 60 minutes. Sessions will be scheduled according to participant preference and medication regimen and conducted during the dopaminergic "ON" state, with rest breaks provided as needed. Participants will be instructed to refrain from other rehabilitation interventions (e.g., exercise, physical therapy, yoga, or cognitive stimulation) during the study period. To identify potential drop-ins (participants who inadvertently or voluntarily receive similar treatments outside the study protocol), a standardized checklist will be administered at each follow-up visit. Any reported external intervention will be documented, and sensitivity analyses will be considered to evaluate its potential impact on study outcomes. Participation may be discontinued at the participant's request at any time.

Measurements Demographic and disease-related data (e.g., age, sex, education, marital and employment status, assistive device use, fall history, disease duration, medication) will be collected at baseline. Outcome assessments will be conducted by a blinded occupational therapist at baseline, post-intervention (6 weeks), and follow-up (12 weeks).

For self-report instruments without prior validation in individuals with cognitive impairment, internal consistency and test-retest reliability were evaluated in a subsample of 40 participants with PD and cognitive impairment, demonstrating acceptable reliability coefficients (Cronbach's α = 0.75-0.90; ICC = 0.81-0.89). If a participant was unable to complete the questionnaire because of severe cognitive impairment or illiteracy, a family member or primary caregiver completed it on their behalf.

Data Analysis All data will be entered and analyzed using IBM SPSS Statistics version 20, with participants assigned unique identifiers to maintain confidentiality. Paper questionnaires and electronic datasets will be securely stored in locked cabinets and password-protected computers. Missing data will be handled using multiple imputation or the last observation carried forward (LOCF) method, depending on the pattern and extent of missingness, and sensitivity analyses will be performed to compare findings across different missing data approaches. Both intention-to-treat (ITT) and per-protocol (PP) analyses will be conducted, with PP designated as the primary analysis and ITT results reported separately if they differ substantially. An interim analysis will be conducted solely for futility monitoring after 45 participants, as described in the sample size calculation. No other interim analyses are planned, and no hypothesis testing will be performed at the interim stage to preserve the type I error rate.

Descriptive statistics will be presented as mean ± SD or median (IQR) for continuous variables, and as frequencies and percentages for categorical variables. Normality will be assessed using the Shapiro-Wilk test, complemented by graphical and numerical methods. Baseline differences between groups will be evaluated using one-way ANOVA or Kruskal-Wallis tests for continuous variables and Chi-square tests for categorical variables. Provided no significant baseline differences exist, primary outcomes will be analyzed using a 3 × 3 mixed factorial ANOVA, with group (occupation-based interventions with or without motivational feedback, conventional care) as the between-subject factor and time (baseline, post-intervention, follow-up) as the within-subject factor. Tukey post hoc tests will be applied for multiple comparisons. All tests will be two-tailed, with significance set at α = 0.05. To address the increased risk of type I error due to multiple secondary outcomes, the Benjamini-Hochberg false discovery rate (FDR) correction will be applied.

To account for intercurrent health events that may influence self-reported outcomes independently of the intervention, all adverse or significant life events occurring during the study period (e.g., falls, injury, hospitalization, acute illness, medication changes, major psychosocial stressors) will be systematically documented at each assessment and follow-up visit using a standardized event log. Information recorded will include event type, timing, severity, duration, and whether it resulted in interruption of treatment or changes in daily functioning.

These events will be considered potential confounders in the analysis. Sensitivity analyses will be conducted excluding participants with major intercurrent events likely to substantially affect quality of life or self-report outcomes. In addition, relevant events (e.g., falls, hospitalization, major medication changes) may be included as time-varying covariates in secondary analyses where appropriate. All analyses will primarily follow the intention-to-treat principle."